Table 3. Fold change in expression of genes downregulated by ≥2.4-fold by JQ1 in CCA2 tumors, compared with CCA1 tumors.

Exposure to JQ1 in vivo downregulated expression of 24 genes by ≥2.4-fold in the relatively sensitive CCA2 tumors. In contrast, JQ1 downregulated only 2 genes to this extent (FAS and FGF2) in a subset of 16 of these 24 genes in CCA1 tumors. These data indicate inhibition of expression of FAS and FGF2 are likely not associated with sensitivity to JQ1 and that expression of BRCA2, WEE1, CDK6, CHEK1, CDK4, MMP9, LFT3, PPARG, E2F1, MSH2, TP53, FGFR2, MYCN, and MYC may be BET-dependent in CCA tumors.

		CCA2			CCA1
Gene	Accession #	JQ1	VC	Fold Change	JQ1	VC	Fold Change
FAS	NM_000043.3	13.23	31.45	−2.38	32.41	82.71	−2.55
BRCA2	NM_000059.3	41.73	102.2	−2.45	1.97	1.97	1
WEE1	NM_003390.2	7.13	17.69	−2.48	508.96	467.08	1.09
CDK6	NM_001259.5	132.33	334.13	−2.53	115.55	189.77	−1.64
MYBL2	NM_002466.2	115.02	294.82	−2.56	Not included
CHEK1	NM_001274.2	91.61	237.82	−2.6	498.43	414.43	1.20
FGR	NM_001042729.1	4.07	10.81	−2.65	Not included
CDK4	NM_000075.2	66.16	192.61	−2.91	572.19	560.1	1.02
MYCL1	NM_001033082.1	7.13	21.62	−3.03	Not included
CTGF	NM_001901.2	492.66	1505.53	−3.06	Not included
CDH11	NM_001797.2	224.95	691.84	−3.08	Not included
MMP9	NM_004994.2	27.48	85.5	−3.11	6.65	9.87	−1.48
FGF2	NM_002006.4	27.48	88.45	−3.22	45.29	144.14	−3.18
FLT3	NM_004119.1	3.05	9.83	−3.22	1.17	1	1.17
PPARG	NM_138711.3	160.83	518.88	−3.23	501.94	512.72	−1.02
E2F1	NM_005225.1	37.66	122.84	−3.26	215.07	248.57	−1.16
MSH2	NM_000251.1	63.11	213.25	−3.38	704.5	579.41	1.22
TP53	NM_000546.2	131.31	479.57	−3.65	127.25	107.28	1.19
FGFR2	NM_000141.4	111.97	410.78	−3.67	123.74	133.61	−1.08
TEK	NM_000459.2	16.29	62.89	−3.86	Not included
LCK	NM_001042771.1	17.3	71.74	−4.15	Not included
MYCN	NM_005378.4	25.45	130.7	−5.14	65.2	59.02	2.25
MYC	NM_002467.3	238.19	1375.81	−5.78	448.08	578.53	−1.29
TIMP3	NM_000362.4	352.19	2565.89	−7.29	Not included